Abstract
DNA polymerase δ (Polδ) is a multisubunit polymerase that plays an indispensable role in replication from yeast to humans. Polδ from Saccharomyces cerevisiae is composed of three subunits: Pol3, Pol31, and Pol32. Despite the elucidation of the structures and models of the individual subunits (or portions, thereof), the nature of their assembly remains unclear. We present here a small-angle X-ray scattering analysis of a yeast Polδ complex (PolδT) composed of Pol3, Pol31, and Pol32N (amino acids 1-103 of Pol32). From the small angle X-ray scattering global parameters and reconstructed envelopes, we show that PolδT adopts an elongated conformation with a radius of gyration (Rg) of ∼ 52 Å and a maximal dimension of ∼ 190 Å. We also propose an orientation for the accessory Pol31-Pol32N subunits relative to the Pol3 catalytic core that best agrees with the experimental scattering profile. The analysis also points to significant conformational variability that may allow Polδ to better coordinate its action with other proteins at the replication fork.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 377-382 |
| Number of pages | 6 |
| Journal | Journal of Molecular Biology |
| Volume | 394 |
| Issue number | 3 |
| DOIs | |
| State | Published - Dec 4 2009 |
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Keywords
- cancer
- DNA polymerase
- DNA replication
- mutagenesis
ASJC Scopus subject areas
- Molecular Biology
Cite this
Structural Insights into Yeast DNA Polymerase δ by Small Angle X-ray Scattering. / Jain, Rinku; Hammel, Michal; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.
In: Journal of Molecular Biology, Vol. 394, No. 3, 04.12.2009, p. 377-382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural Insights into Yeast DNA Polymerase δ by Small Angle X-ray Scattering
AU - Jain, Rinku
AU - Hammel, Michal
AU - Johnson, Robert E.
AU - Prakash, Louise
AU - Prakash, Satya
AU - Aggarwal, Aneel K.
PY - 2009/12/4
Y1 - 2009/12/4
N2 - DNA polymerase δ (Polδ) is a multisubunit polymerase that plays an indispensable role in replication from yeast to humans. Polδ from Saccharomyces cerevisiae is composed of three subunits: Pol3, Pol31, and Pol32. Despite the elucidation of the structures and models of the individual subunits (or portions, thereof), the nature of their assembly remains unclear. We present here a small-angle X-ray scattering analysis of a yeast Polδ complex (PolδT) composed of Pol3, Pol31, and Pol32N (amino acids 1-103 of Pol32). From the small angle X-ray scattering global parameters and reconstructed envelopes, we show that PolδT adopts an elongated conformation with a radius of gyration (Rg) of ∼ 52 Å and a maximal dimension of ∼ 190 Å. We also propose an orientation for the accessory Pol31-Pol32N subunits relative to the Pol3 catalytic core that best agrees with the experimental scattering profile. The analysis also points to significant conformational variability that may allow Polδ to better coordinate its action with other proteins at the replication fork.
AB - DNA polymerase δ (Polδ) is a multisubunit polymerase that plays an indispensable role in replication from yeast to humans. Polδ from Saccharomyces cerevisiae is composed of three subunits: Pol3, Pol31, and Pol32. Despite the elucidation of the structures and models of the individual subunits (or portions, thereof), the nature of their assembly remains unclear. We present here a small-angle X-ray scattering analysis of a yeast Polδ complex (PolδT) composed of Pol3, Pol31, and Pol32N (amino acids 1-103 of Pol32). From the small angle X-ray scattering global parameters and reconstructed envelopes, we show that PolδT adopts an elongated conformation with a radius of gyration (Rg) of ∼ 52 Å and a maximal dimension of ∼ 190 Å. We also propose an orientation for the accessory Pol31-Pol32N subunits relative to the Pol3 catalytic core that best agrees with the experimental scattering profile. The analysis also points to significant conformational variability that may allow Polδ to better coordinate its action with other proteins at the replication fork.
KW - cancer
KW - DNA polymerase
KW - DNA replication
KW - mutagenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=70350704561&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2009.09.066
DO - 10.1016/j.jmb.2009.09.066
M3 - Article
VL - 394
SP - 377
EP - 382
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 3
ER -